Low-level lead exposure triggers neuronal apoptosis in the developing mouse brain

Neurotoxicology and Teratology

Volumn 33, Issue 4, 2011, Pages 473-480

  Dribben, William H ^a   Creeley, Catherine E ^a   Farber, Nuri ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; Lead; Neurodevelopment; Neurotoxicity; NMDA antagonist

Indexed keywords

CASPASE 3; LEAD;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BRAIN CORTEX; BRAIN DEVELOPMENT; BRAIN NERVE CELL; CAUDATE NUCLEUS; CELL ULTRASTRUCTURE; CONTROLLED STUDY; ELECTRON MICROSCOPY; ENZYME ACTIVATION; EXPOSURE; FRONTAL CORTEX; HIPPOCAMPUS; HISTOLOGY; IMMUNOHISTOCHEMISTRY; MOUSE; NERVE DEGENERATION; NEUROTOXICITY; NEWBORN; NISSL STAINING; NONHUMAN; PERINATAL PERIOD; PRIORITY JOURNAL; PUTAMEN; SILVER STAINING; SUBICULUM;

ANIMALS; ANIMALS, NEWBORN; APOPTOSIS; BRAIN; CASPASE 3; CELL COUNT; DOSE-RESPONSE RELATIONSHIP, DRUG; ENVIRONMENTAL POLLUTANTS; IMMUNOHISTOCHEMISTRY; LEAD; MICE; MICE, INBRED C57BL; MICROSCOPY, ELECTRON, TRANSMISSION; NEURONS;

ANIMALIA; MUS;

EID: 79960629364     PISSN: 08920362     EISSN: 18729738     Source Type: Journal    
DOI: 10.1016/j.ntt.2011.05.006     Document Type: Article

References (68)

1. Anastasio N.C., Xia Y., O'Connor Z.R., Johnson K.M. Differential role of N-methyl-D-aspartate receptor subunits 2A and 2B in mediating phencyclidine-induced perinatal neuronal apoptosis and behavioral deficits. Neuroscience 2009, 163:1181-1191.
2. Audesirk G. Electrophysiology of lead intoxication: effects on voltage-sensitive ion channels. Neurotoxicology 1993, 14:137-147.
3. Baghurst P.A., Tong S., Sawyer M.G., Burns J., McMichael A.J. Environmental exposure to lead and children's intelligence at the age of seven years. The Port Pirie Cohort Study. N Engl J Med 1992, 327:1279-1284.
4. Bellinger D.C. Lead. Pediatrics 2004, 113:1016-1022.
5. Binns H.J., Campbell C., Brown M.J. Centers for Disease Control and Prevention Advisory Committee on Childhood Lead Poisoning Prevention. Interpreting and managing blood lead levels of less than 10 microg/dL in children and reducing childhood exposure to lead: recommendations of the Centers for Disease Control and Prevention Advisory Committee on Childhood Lead Poisoning Prevention. Pediatrics 2007, 120:e1285-e1298.
6. Bouldin T.W., Krigman M.R. Acute lead encephalopathy in the guinea pig. Acta Neuropathol 1975, 33(3):185-190.
7. Brockel B.J., Cory-Slechta D.A. Lead, attention, and impulsive behavior: changes in a fixed-ratio waiting-for-reward paradigm. Pharmacol Biochem Behav 1998, 60:545-552.
8. Busselberg D. Calcium channels as target sites of heavy metals. Toxicol Lett 1995, 82-83:255-261.
9. Canfield R.L., Henderson C.R., Cory-Slechta D.A., Cox C., Jusko T.A., Lanphear B.P. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med 2003, 348:1517-1526.
10. Canfield R.L., Kreher D.A., Cornwell C., Henderson C.R. Low-level lead exposure, executive functioning, and learning in early childhood. Child Neuropsychol 2003, 9:35-53.
11. Carpenter D.O., Matthews M.R., Parsons P.J., Hori N. Long-term potentiation in the piriform cortex is blocked by lead. Cell Mol Neurobiol 1994, 14:723-733.
12. Chiodo L.M., Jacobson S.W., Jacobson J.L. Neurodevelopmental effects of postnatal lead exposure at very low levels. Neurotoxicol Teratol 2004, 26:359-371.
13. Chisolm J.J. Evolution of the management and prevention of childhood lead poisoning: dependence of advances in public health on technological advances in the determination of lead and related biochemical indicators of its toxicity. Environ Res 2001, 86:111-121.
14. Chisolm J.J. The road to primary prevention of lead toxicity in children. Pediatrics 2001, 107:581-583.
15. Corso T.D., Sesma M.A., Tenkova T.I., Der T.C., Wozniak D.F., Farber N.B., et al. Multifocal brain damage induced by phencyclidine is augmented by pilocarpine. Brain Res 1997, 752:1-14.
16. Cremin J.D. Smith DR. In vitro vs. in vivo Pb effects on brain protein kinase C activity. Environ Res 2002, 90:191-199.
17. DeOlmos J.S., Ingram W.R. An improved cupric-silver method for impregnation of axonal and terminal degeneration. Brain Res 1971, 33:523-529.
18. Dikranian K., Ishimaru M.J., Tenkova T., Labruyere J., Qin Y.Q., Ikonomidou C., et al. Apoptosis in the in vivo mammalian forebrain. Neurobiol Dis 2001, 8:359-379.
19. Dikranian K., Qin Y.Q., Labruyere J., Nemmers B., Olney J.W. Ethanol-induced neuroapoptosis in the developing rodent cerebellum and related brain stem structures. Brain Res Dev Brain Res 2005, 155:1-13.
20. Dobbing J., Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev 1979, 3:79-83.
21. Dribben W.H., Creeley C.E., Wang H.H., Smith D.J., Farber N.B., Olney J.W. High dose magnesium sulfate exposure induces apoptotic cell death in the developing neonatal mouse brain. Neonatology 2009, 96:23-32.
22. Farber N.B., Creeley C.E., Olney J.W. Alcohol-induced neuroapoptosis in the fetal macaque brain. Neurobiol Dis 2010, 40:200-206.
23. Fox D.A., Campbell M.L., Blocker Y.S. Functional alterations and apoptotic cell death in the retina following developmental or adult lead exposure. Neurotoxicology 1997, 18:645-664.
24. Fredriksson A., Archer T. Neurobehavioural deficits associated with apoptotic neurodegeneration and vulnerability for ADHD. Neurotox Res 2004, 6:435-456.
25. Fredriksson A., Pontén E., Gordh T., Eriksson P. Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits. Anesthesiology 2007, 107:427-436.
26. Goldstein G.W. Evidence that lead acts as a calcium substitute in second messenger metabolism. Neurotoxicology 1993, 14:97-101.
27. Guilarte T.R. Glutamatergic system and developmental lead neurotoxicity. Neurotoxicology 1997, 18:665-672.
28. Guilarte T.R., McGlothan J.L. Hippocampal NMDA receptor mRNA undergoes subunit specific changes during developmental lead exposure. Brain Res 1998, 790:98-107.
29. Guilarte T.R., McGlothan J.L. Selective decrease in NR1 subunit splice variant mRNA in the hippocampus of Pb2+-exposed rats: implications for synaptic targeting and cell surface expression of NMDAR complexes. Brain Res Mol Brain Res 2003, 113:37-43.
30. Guilarte T.R., Miceli R.C. Age-dependent effects of lead on [3H]MK-801 binding to the NMDA receptor-gated ionophore: in vitro and in vivo studies. Neurosci Lett 1992, 148:27-30.
31. Guilarte T.R., Miceli R.C., Jett D.A. Neurochemical aspects of hippocampal and cortical Pb2+ neurotoxicity. Neurotoxicology 1994, 15:459-466.
32. Guilarte T.R., Miceli R.C., Jett D.A. Biochemical evidence of an interaction of lead at the zinc allosteric sites of the NMDA receptor complex: effects of neuronal development. Neurotoxicology 1995, 16:63-71.
33. Gundersen H.J., Bagger P., Bendtsen T.F., et al. The new stereological tools: dissector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 1988, 96:857-881.
34. Hansen H.H., Briem T., Dzietko M., Sifringer M., Voss A., Rzeski W., et al. Mechanisms leading to disseminated apoptosis following NMDA receptor blockade in the developing rat brain. Neurobiol Dis 2004, 16:440-453.
35. He L., Poblenz A.T., Medrano C.J., Fox D.A. Lead and calcium produce rod photoreceptor cell apoptosis by opening the mitochondrial permeability transition pore. J Biol Chem 2000, 275:12175-12184.
36. Ikonomidou C., Bosch F., Miksa M., Bittigau P., Vöckler J., Dikranian K., et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999, 283:70-74.
37. Kerper L.E., Hinkle P.M. Cellular uptake of lead is activated by depletion of intracellular calcium stores. J Biol Chem 1997, 272:8346-8352.
38. Komuro H., Rakic P. Modulation of neuronal migration by NMDA receptors. Science 1993, 260:95-97.
39. Lanphear B.P., Hornung R., Khoury J., Yolton K., Baghurst P., Bellinger D.C., et al. Low-level environmental lead exposure and children's intellectual function: an international pooled analysis. Environ Health Perspect 2005, 113:894-899.
40. Lasley S.M., Green M.C., Gilbert M.E. Rat hippocampal NMDA receptor binding as a function of chronic lead exposure level. Neurotoxicol Teratol 2001, 23:185-189.
41. Lewis J. Lead Poisoning: A Historical Perspective. EPA Journal 1985, Accessed online at, September 13, 2010. http://www.epa.gov/history/topics/perspect/lead.htm.
42. Liu J., Han D., Li Y., Zheng L., Gu C., Piao Z., et al. Lead affects apoptosis and related gene XIAP and Smac expression in the hippocampus of developing rats. Neurochem Res 2010, 35:473-479.
43. Lorenzo A.V., Gewirtz M., Averill D. CNS lead toxicity in rabbit offspring. Environ Res 1978, 17:131-150.
44. Lyall A., Swanson J., Liu C., Blumenthal T.D., Turner C.P. Neonatal exposure to MK801 promotes prepulse-induced delay in startle response time in adult rats. Exp Brain Res 2009, 197:215-222.
45. Markowitz G., Rosner D. Cater to the children: the role of the lead industry in a public health tragedy, 1900-1955. Am J Public Health 2000, 90:36-46.
46. McCauley P.T., Bull R.J., Tonti A.P., Lutkenhoff S.D., Meister M.V., Doerger J.U., et al. The effect of prenatal and postnatal lead exposure on neonatal synaptogenesis in rat cerebral cortex. J Toxicol Environ Health 1982, 10:639-651.
47. Moreira E.G., Vassilieff I., Vassilieff V.S. Developmental lead exposure: behavioral alterations in the short and long term. Neurotoxicol Teratol 2001, 23:489-495.
48. Olney J.W., Tenkova T., Dikranian K., Muglia L.J., Jermakowicz W.J., D'Sa C., et al. Ethanol-induced caspase-3 activation in the in vivo developing mouse brain. Neurobiol Dis 2002, 9:205-219.
49. Peng S., Hajela R.K., Atchison W.D. Characteristics of block by Pb2+ of function of human neuronal L-, N-, and R-type Ca2+ channels transiently expressed in human embryonic kidney 293 cells. Mol Pharmacol 2002, 62:1418-1430.
50. Press M.F. Lead encephalopathy in neonatal Long-Evans rats: morphologic studies. J Neuropathol Exp Neurol 1977, 36:169-193.
51. Rice D., Barone S. Critical periods of vulnerability for the developing nervous system: evidence from human and animal models. Environ Health Perspect 2000, 535-544. 108S3.
52. Schulte S., Muller W.E., Friedberg K.D. In vitro and in vivo effects of lead on specific 3H-PN200-110 binding to dihydropyridine receptors in the frontal cortex of the mouse brain. Toxicology 1995, 97:113-121.
53. Simons T.J. Lead-calcium interactions in cellular lead toxicity. Neurotoxicology 1993, 14:77-85.
54. Slikker W., Zou X., Hotchkiss C.E., Divine R.L., Sadovova N., Twaddle N.C., et al. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci 2007, 98:145-158.
55. Soriano S.G., Liu Q., Li J., Liu J.R., Han X.H., Kanter J.L., et al. Ketamine activates cell cycle signaling and apoptosis in the neonatal rat brain. Anesthesiology 2010, 112:1155-1163.
56. Struzynska L., Walski M., Gadamski R., Dabrowska-Bouta B., Rafalowska U. Lead-induced abnormalities in blood-brain barrier permeability in experimental chronic toxicity. Mol Chem Neuropathol 1997, 31(3):207-224.
57. Toscano C.D., Hashemzadeh-Gargari H., McGlothan J.L., Guilarte T.R. Developmental Pb2+ exposure alters NMDAR subtypes and reduces CREB phosphorylation in the rat brain. Brain Res Dev Brain Res 2002, 139:217-226.
58. West M.J., Slomainka L., Gundersen H.J. Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 1991, 231:482-497.
59. White L.D., Cory-Slechta D.A., Gilbert M.E., Tiffany-Castiglioni E., Zawia N.H., Virgolini M., et al. New and evolving concepts in the neurotoxicology of lead. Toxicol Appl Pharmacol 2007, 225:1-27.
60. Winder C., Garten L.L., Lewis P.D. The morphological effects of lead on the developing central nervous system. Neuropathol Appl Neurobiol 1983, 9:87-108.
61. Winneke G., Lilienthal H., Krämer U. The neurobehavioural toxicology and teratology of lead. Arch Toxicol Suppl 1996, 18:57-70.
62. Wozniak D.F., Hartman R.E., Boyle M.P., Vogt S.K., Brooks A.R., Tenkova T., et al. Apoptotic neurodegeneration induced by ethanol in neonatal mice is associated with profound learning/memory deficits in juveniles followed by progressive functional recovery in adults. Neurobiol Dis 2004, 17:403-414.
63. Xu J., Ji L.D., Xu L.H. Lead-induced apoptosis in PC 12 cells: involvement of p53, Bcl-2 family and caspase-3. Toxicol Lett 2006, 166:160-167.
64. Young C., Roth K.A., Klocke B.J., West T., Holtzman D.M., Labruyere J., et al. Role of caspase-3 in ethanol-induced developmental neurodegeneration. Neurobiol Dis 2005, 20:608-614.
65. Young C., Straiko M.M., Johnson S.A., Creeley C., Olney J.W. Ethanol causes and lithium prevents neuroapoptosis and suppression of pERK in the infant mouse brain. Neurobiol Dis 2008, 31:355-360.
66. Yuede C.M., Wozniak D.F., Creeley C.E., Taylor G.T., Olney J.W., Farber N.B. Behavioral consequences of NMDA antagonist-induced neuroapoptosis in the infant mouse brain. PLoS One 2010, 5:e11374.
67. Zhang X.Y., Liu A.P., Ruan D.Y., Liu J. Effect of developmental lead exposure on the expression of specific NMDA receptor subunit mRNAs in the hippocampus of neonatal rats by digoxigenin-labeled in situ hybridization histochemistry. Neurotoxicol Teratol 2002, 24:149-160.
68. Zou X., Patterson T.A., Divine R.L., Sadovova N., Zhang X., Hanig J.P., et al. Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain. Int J Dev Neurosci 2009, 27:727-731.